Human Monoclonal Antibodies EV1018 EV1019 Neutralize hGM-CSF
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Solution Overview
Problem
Current anti-human Granulocyte-Macrophage Colony Stimulating Factor (hGM-CSF) monoclonal antibodies lack sufficient neutralizing activity and often induce immunological reactions due to non-human origins, posing safety concerns and inefficacy in treating diseases associated with hGM-CSF over-expression.
Innovation Solution
Development of highly specific and potent human monoclonal antibodies, such as EV1018 and EV1019, which bind to hGM-CSF with exceptionally high affinity and neutralizing capacity, minimizing immunogenicity and leveraging specific epitope recognition to inhibit hGM-CSF activity effectively.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If presently-available anti-hGM-CSF monoclonal antibodies are used, then binding to hGM-CSF is achieved, but neutralizing activity is insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's binding characteristics and neutralizing capacity through selective screening and characterization. The inventors identified antibodies with specific binding parameters that achieve both high affinity (KD < 400 pM) and superior neutralizing activity (IC50 < 100 pM) by changing the selection criteria and evaluation parameters during antibody development
Solution Approach 2:
The patent replaces conventional antibody production methods with phage display technology, substituting traditional mechanical/biological screening processes with a molecular display system that allows direct selection of antibodies possessing both high binding affinity and high neutralizing activity against hGM-CSF
2Reliability
If polyclonal or monoclonal antibodies from experimental animals are administered, then hGM-CSF binding is achieved, but human anti-animal antibody response is induced
Solution Approach 1:
The patent changes the origin parameter of the antibody from animal-derived to human-derived through phage display technology using human antibody repertoires. This parameter change eliminates immunogenicity while preserving binding capability, as the human immune system does not recognize human antibodies as foreign antigens
Solution Approach 2:
The patent uses phage display technology as an intermediary system to select and produce human antibodies. The phage display platform serves as a mediator that allows screening of human antibody sequences without requiring animal immunization, thus avoiding the introduction of animal protein sequences that would trigger human anti-animal antibody responses
3Duration of action of moving object
If long-term administration of antibodies is performed, then treatment effectiveness is maintained, but safety problems arise from impurities
Solution Approach 1:
The patent replaces conventional animal antibody production and purification processes with phage display-based human antibody selection and recombinant production. This substitution enables manufacturing of highly pure human antibodies with defined sequences, eliminating impurities associated with animal-derived products and enabling safe long-term administration
Solution Approach 2:
The patent employs human antibodies that are inherently compatible with the human immune system, allowing them to serve themselves by avoiding immunogenicity issues. The human origin of the antibodies means they do not trigger immune responses against foreign proteins, enabling self-compatible long-term therapy without the safety concerns associated with animal-derived antibody impurities
Data Source
AI summary
Disclosed herein are anti-hGM-CSF monoclonal antibodies and antigen-binding fragments of such antibodies, with improved neutralizing capacity to hGM-CSF activity. Pharmaceutical compositions comprising such an antibody or antigen-binding fragment are also provided. The present invention is useful for the treatment of various diseases that are associated with aberrant expression of hGM-CSF.